CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation
- Authors
- Kim, Hyun-Yi; Yang, Dong-Hwa; Shin, Song-Weon; Kim, Mi-Yeon; Yoon, Jae-Hyun; Kim, Suhyun; Park, Hae-Chul; Kang, Dong Woo; Min, DoSik; Hur, Man-Wook; Choi, Kang-Yell
- Issue Date
- 2월-2014
- Publisher
- FEDERATION AMER SOC EXP BIOL
- Keywords
- HUVECs; mouse embryonic stem cells; caudal vein plex vessel formation
- Citation
- FASEB JOURNAL, v.28, no.2, pp.615 - 626
- Indexed
- SCIE
SCOPUS
- Journal Title
- FASEB JOURNAL
- Volume
- 28
- Number
- 2
- Start Page
- 615
- End Page
- 626
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/99457
- DOI
- 10.1096/fj.13-236216
- ISSN
- 0892-6638
- Abstract
- CXXC5 is a member of a small subset of proteins containing CXXC-type zinc-finger domain. Here, we show that CXXC5 is a transcription factor activating Flk-1, a receptor for vascular endothelial growth factor. CXXC5 and Flk-1 were accmulated in nucli and membrane of mouse embryonic stem cells (mESCs), respectively, during their endothelial differentiation. CXXC5 overexpression induced Flk-1 transcription in both endothelium-differentiated mESCs and human umbilical vein endothelial cells (HUVECs). In vitro DNA binding assay showed direct interaction of CXXC5 on the Flk-1 promoter region, and mutation on its DNA-binding motif abolished transcriptional activity. We showed that bone morphorgeneic protein 4 (BMP4) induced CXXC5 transcription in the cells, and inhibitors of BMP signaling suppressed the CXXC5 induction and the consequent Flk-1 induction by BMP4 treatment. CXXC5 knockdown resulted in suppression of BMP4-induced stress fiber formation (56.8 +/- 1.3% decrease, P<0.05) and migration (54.6 +/- 1.9% decrease, P<0.05) in HUVECs. The in vivo roles of CXXC5 in BMP-signaling-specific vascular development and angiogenesis were shown by specific defect of caudal vein plex vessel formation (57.9 +/- 11.8% decrease, P<0.05) in cxxc5 morpholino-injected zebrafish embryos and by supression of BMP4-induced angigogensis in subcutaneously injected Matrigel plugs in CXXC5(-/-) mice. Overall, CXXC5 is a transcriptional activator for Flk-1, mediating BMP signaling for differentiation and migration of endothelial cell and vessel formation.Kim, H.-Y., Yang, D.-H., Shin, S.-W., Kim, M.-Y., Yoon, J.-H., Kim, S., Park, H.-C., Kang, D. W., Min, D., Hur, M.-W., Choi, K.-Y. CXXC5 is a transcriptional activator of Flk-1 and mediates bone morphogenic protein-induced endothelial cell differentiation and vessel formation.
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Collections - Graduate School > Department of Biomedical Sciences > 1. Journal Articles
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